Navigation Links
New target for maintaining healthy blood pressure discovered
Date:4/24/2009

PHILADELPHIA - In trying to understand the role of prostaglandins a family of fatty compounds key to the cardiovascular system in blood pressure maintenance, researchers at the University of Pennsylvania School of Medicine and colleagues discovered that mice that lack the receptor for one type of prostaglandin have lower blood pressure and less atherosclerosis than their non-mutant brethren.

The results indicate that the normal role for the type of prostaglandin studied, PG F2-alphais to increase blood pressure and accelerate atherosclerosis, at least in rodents, and suggest that targeting this pathway could represent a novel therapeutic approach to cardiovascular disease.

The results appeared this week in the Proceedings of the National Academy of Sciences.

"Blocking this prostaglandin receptor may provide a strategy for controlling blood pressure and its attendant vascular disease," notes senior author Garret A. FitzGerald, MD, Director of the Institute for Translational Medicine and Therapeutics at Penn.

To address prostaglandins' role in maintaining blood pressure, FitzGerald and his team, including researchers from the University of Southern Denmark, created strains of mice in which both the maternal and paternal copies of the gene for the PG F2-alphareceptor were deleted. They did this in mice with a normal genetic background and in ones that contained an additional mutation in the low-density lipoprotein receptor gene. These manipulations effectively rendered the mice unable to respond to the prostaglandins.

The delicate balance the body maintains to keep blood pressure stable involves not only the prostaglandin system, but another biological pathway, the renin-angiotensin-aldosterone system, or RAAS. Under conditions of low blood pressure, the liver secretes a protein called angiotensiogen. Renin, an enzyme produced by the kidneys, cleaves angiotensiogen into a peptide called angiotensin I. Angiotensin I is cleaved again to form angiotensin II, which stimulates blood vessels to narrow, thereby increasing blood pressure. At the same time, angiotensin II induces the release of the hormone aldosterone, which further elevates blood pressure by promoting retention of water and sodium in the kidneys.

Many conventional therapies for high blood pressure target components of the RAAS pathway. For instance, ACE inhibitors such as captopril (Capoten) target the formation of angiotensin II, while aliskiren (Tekturna) targets renin.

The team assessed the impact of the PG F2-alpha receptor mutations on both blood pressure and RAAS activity. They found that under a variety of circumstances deletion of the PG F2-alpha receptor lowered blood pressure coincident with suppression of RAAS activity.

"Precisely how these two observations are connected is the focus of our current research," says FitzGerald.

Blood pressure was reduced in both types of genetically engineered mice relative to control littermates. The RAAS molecules renin, angiotensin I, and aldosterone were also reduced, a biological situation leading to lower blood pressure.

The team found that the PG F2-alpha receptor is expressed in the smooth muscle surrounding arteries in the kidneys. However, it was absent in the muscle surrounding the aorta, in the atherosclerotic lesions of mice with their PG F2-alphareceptors knocked out, as well as in the macrophages that inhabit those lesions. Importantly, these atherosclerotic lesions were smaller and less abundant in mice that had both the low-density lipoprotein and PG F2-alpha receptors knocked out, as was macrophage infiltration and inflammatory cytokine production, both of which are indicators of the inflammatory response that marks these plaques.

Prostaglandins are produced during the oxidation of certain cell molecules by cyclooxygenases, the COX enzymes targeted by COX inhibitors, but how remains unclear. FitzGerald's group had previously shown that blockading cyclooxygenase 1 and its major prostaglandin product, thromboxane, also lowers blood pressure, slowing atherosclerosis, but in this previous study, the relevant genes are present in the aorta and its atherosclerotic lesions. PG F2-alpha by contrast, acts via the kidney and represents a distinct therapeutic opportunity.

"The picture is emerging that PG F2-alpha controls blood pressure by a mechanism unique among the prostaglandins," says FitzGerald. "Besides the case of thromboxane, two other types of prostaglandins, PGI2 and PGE2, stimulate renin secretion, which is part of the RAAS pathway."

Assuming these findings can be translated to humans, targeting the PG F2-alpha pathway could represent a novel opportunity for therapeutic control of blood pressure in cardiovascular patients.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Targeted agent shows promise in biliary cancer study
2. USC researchers develop new drug to target tumor cells and blood vessels
3. Targeted Treatments Show Mettle Against Advanced Cancers
4. AMDL, Inc. Reports 2008 Year End Financial Results and Fiscal Year 2009 Financial Targets
5. UCSF, Stanford Study Reveals Neural Networks Targeted in Brain Diseases
6. Test quickly assesses whether Alzheimers drugs are hitting their target
7. A potential new target for treatment of hormone refractory prostate cancer
8. Cellular target may prove useful in treating deadly brain tumors
9. Treatment Target for Herpes Pinpointed
10. Targeting oxidized cysteine through diet could reduce inflammation and lower disease risk
11. Biotech company cofounded by BIDMC scientists targets natural killer T-cells
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New target for maintaining healthy blood pressure discovered
(Date:6/26/2016)... ... June 27, 2016 , ... Quality metrics are proliferating in cancer care, ... remain in the eye of the beholder, according to experts who offered insights and ... Journal of Managed Care. For the full issue, click here . , For ...
(Date:6/26/2016)... Cary, North Carolina (PRWEB) , ... June 26, 2016 , ... ... the release of a new product that was developed to enhance the health of ... harvested for centuries. , The two main herbs in the PawPaws Cat Kidney ...
(Date:6/25/2016)... ... June 25, 2016 , ... Experts from the American ... Annual Research Meeting June 26-28, 2016, at the Hynes Convention Center in Boston. ... including advance care planning, healthcare costs and patient and family engagement. , AIR ...
(Date:6/25/2016)... Aliso Viejo, California (PRWEB) , ... June 25, 2016 , ... ... preset to fit their specific project," said Christina Austin - CEO of Pixel Film ... all fully customizable and all within Final Cut Pro X . Simply select ...
(Date:6/25/2016)... Oklahoma City, Oklahoma (PRWEB) , ... June 25, ... ... to helping both athletes and non-athletes recover from injury. Recently, he has implemented ... for the Oklahoma City area —Johnson is one of the first doctors to ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016  Collagen Matrix, ... design, development and manufacturing of collagen and mineral ... announced today that Bill Messer has ... Marketing to further leverage the growing portfolio of ... devices. Bill joins the Collagen Matrix ...
(Date:6/24/2016)... -- The Academy of Managed Care Pharmacy (AMCP) today ... allow biopharmaceutical companies to more easily share health care ... coverage decisions, a move that addresses the growing need ... The recommendations address restrictions in the sharing of product ... a prohibition that hinders decision makers from accessing HCEI ...
(Date:6/24/2016)... 2016   Pulmatrix, Inc ., (NASDAQ: ... drugs, announced today that it was added to the ... its comprehensive set of U.S. and global equity indexes ... important milestone for Pulmatrix," said Chief Executive Officer ... our progress in developing drugs for crucial unmet medical ...
Breaking Medicine Technology: